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1. chinaXiv:201605.01809 [pdf]

BMP2-SMAD Signaling Represses the Proliferation of Embryonic Neural Stem Cells through YAP

Yao, Minghui; Wang, Yadong; Zhang, Peng; Chen, Hong; Yuan, Zengqiang; Yao, Minghui; Xu, Zhiheng; Jiao, Jianwei; Wang, Yadong
Subjects: Biology >> Biophysics >> Neurosciences

Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.

submitted time 2016-06-06 Hits3937Downloads1694 Comment 0

2. chinaXiv:201605.01805 [pdf]

Attention-Dependent Early Cortical Suppression Contributes to Crowding

Chen, Juan; He, Yingchen; Zhu, Ziyun; Peng, Yujia; Zhang, Xilin; Fang, Fang; Chen, Juan; He, Yingchen; Zhu, Ziyun; Peng, Yujia; Zhang, Xilin; Fang, Fang; Fang, Fang; Fang, Fang; Zhou, Tiangang
Subjects: Biology >> Biophysics >> Neurosciences

Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing.

submitted time 2016-05-18 Hits3560Downloads1946 Comment 0

3. chinaXiv:201605.01490 [pdf]

Prefrontal dysfunction and a monkey model of schizophrenia

Ma, Yuan-Ye; Mao, Ping; Cui, Ding; Zhao, Xu-Dong; Ma, Yuan-Ye; Ma, Yuan-Ye
Subjects: Biology >> Biophysics >> Neurosciences

The prefrontal cortex is implicated in cognitive functioning and schizophrenia. Prefrontal dysfunction is closely associated with the symptoms of schizophrenia. In addition to the features typical of schizophrenia, patients also present with aspects of cognitive disorders. Based on these relationships, a monkey model mimicking the cognitive symptoms of schizophrenia has been made using treatment with the non-specific competitive N-methyl-D-aspartate receptor antagonist, phencyclidine. The symptoms are ameliorated by atypical antipsychotic drugs such as clozapine. The beneficial effects of clozapine on behavioral impairment might be a specific indicator of schizophrenia-related cognitive impairment.

submitted time 2016-05-12 Hits3082Downloads1477 Comment 0

4. chinaXiv:201605.01473 [pdf]

Layer-specific response properties of the human lateral geniculate nucleus and superior colliculus

Zhang, Peng; Zhou, Hao; He, Sheng; Wen, Wen; He, Sheng
Subjects: Biology >> Biophysics >> Neurosciences

The human LGN and SC consist of distinct layers, but their layer-specific response properties remain poorly understood. In this fMRI study, we characterized visual response properties of the magnocellular (M) and parvocellular (P) layers of the human LGN, as well as at different depths in the SC. Results show that fMRI is capable of resolving layer-specific signals from the LGN and SC. Compared to the P layers of the LGN, the M layers preferred higher temporal frequency, lower spatial frequency stimuli, and their responses saturated at lower contrast. Furthermore, the M layers are colorblind while the P layers showed robust response to both chromatic and achromatic stimuli. Visual responses in the SC were strongest in the superficial voxels, which showed similar spatiotemporal and contrast response properties as the M layers of the LGN, but were sensitive to color and responded strongly to isoluminant color stimulus. Thus, the non-invasive fMRI measures show that the M and P layers of human LGN have similar response properties as that observed in non-human primates and the superficial layers of the human SC prefer transient inputs but are not colorblind. (C) 2015 Elsevier Inc. All rights reserved.

submitted time 2016-05-12 Hits3496Downloads1561 Comment 0

5. chinaXiv:201605.01460 [pdf]

Behavioral Oscillation in Priming: Competing Perceptual Predictions Conveyed in Alternating Theta-Band Rhythms

Huang, Yan; Chen, Lin; Luo, Huan; Luo, Huan
Subjects: Biology >> Biophysics >> Neurosciences

The brain constantly creates perceptual predictions about forthcoming stimuli to guide perception efficiently. Abundant studies have demonstrated that perceptual predictions modulate sensory activities depending on whether the actual inputs are consistent with one particular prediction. In real-life contexts, however, multiple and even conflicting predictions might concurrently exist to be tested, requiring a multiprediction coordination process. It remains largely unknown how multiple hypotheses are conveyed and harmonized to guide moment-by-moment perception. Based on recent findings revealing that multiple locations are sampled alternatively in various phase of attentional rhythms, we hypothesize that this oscillation-based temporal organization mechanism may also underlie the multiprediction coordination process. To address the issue, we used well established priming paradigms in combination with a time-resolved behavioral approach to investigate the fine temporal dynamics of the multiprediction harmonization course in human subjects. We first replicate classical priming effects in slowly developing trends of priming time courses. Second, after removing the typical priming patterns, we reveal a new theta-band (similar to 4 Hz) oscillatory component in the priming behavioral data regardless of whether the prime was masked. Third, we show that these theta-band priming oscillations triggered by congruent and incongruent primes are in an out-of-phase relationship. These findings suggest that perceptual predictions return to low-sensory areas not continuously but recurrently in a theta-band rhythm (every 200-300 ms) and that multiple predictions are dynamically coordinated in time by being conveyed in different phases of the theta-band oscillations to achieve dissociated but temporally organized neural representations.

submitted time 2016-05-12 Hits3054Downloads1365 Comment 0

6. chinaXiv:201605.01393 [pdf]

A conditioned visual orientation requires the ellipsoid body in Drosophila

Guo, Chao; Du, Yifei; Yuan, Deliang; Li, Meixia; Gong, Haiyun; Gong, Zhefeng; Liu, Li; Guo, Chao; Du, Yifei; Yuan, Deliang; Liu, Li
Subjects: Biology >> Biophysics >> Neurosciences

Orientation, the spatial organization of animal behavior, is an essential faculty of animals. Bacteria and lower animals such as insects exhibit taxis, innate orientation behavior, directly toward or away from a directional cue. Organisms can also orient themselves at a specific angle relative to the cues. In this study, using Drosophila as a model system, we established a visual orientation conditioning paradigm based on a flight simulator in which a stationary flying fly could control the rotation of a visual object. By coupling aversive heat shocks to a fly's orientation toward one side of the visual object, we found that the fly could be conditioned to orientate toward the left or right side of the frontal visual object and retain this conditioned visual orientation. The lower and upper visual fields have different roles in conditioned visual orientation. Transfer experiments showed that conditioned visual orientation could generalize between visual targets of different sizes, compactness, or vertical positions, but not of contour orientation. Rut-Type I adenylyl cyclase and Dnc-phosphodiesterase were dispensable for visual orientation conditioning. Normal activity and scb signaling in R3/R4d neurons of the ellipsoid body were required for visual orientation conditioning. Our studies established a visual orientation conditioning paradigm and examined the behavioral properties and neural circuitry of visual orientation, an important component of the insect's spatial navigation.

submitted time 2016-05-12 Hits3084Downloads1366 Comment 0

7. chinaXiv:201605.01366 [pdf]

Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning

Chen, Nihong; Li, Sheng; Fang, Fang; Chen, Nihong; Li, Sheng; Fang, Fang; Chen, Nihong; Li, Sheng; Fang, Fang; Chen, Nihong; Fang, Fang; Bi, Taiyong; Bi, Taiyong; Zhou, Tiangang; Liu, Zili
Subjects: Biology >> Biophysics >> Neurosciences

Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decisionmaking area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. (C) 2015 Elsevier Inc. All rights reserved.

submitted time 2016-05-12 Hits2974Downloads1484 Comment 0

8. chinaXiv:201605.01348 [pdf]

A Portion of Inhibitory Neurons in Human Temporal Lobe Epilepsy are Functionally Upregulated: An Endogenous Mechanism for Seizure Termination

Wen, Bo; Qian, Hao; Feng, Jing; Ge, Rong-Jing; Wang, Jin-Hui; Wen, Bo; Qian, Hao; Wang, Jin-Hui; Ge, Rong-Jing; Xu, Xin; Cui, Zhi-Qiang; Zhu, Ru-Yuan; Pan, Long-Sheng; Lin, Zhi-Pei
Subjects: Biology >> Biophysics >> Neurosciences

Main ProblemEpilepsy is one of the more common neurological disorders. The medication is often ineffective to the patients suffering from intractable temporal lobe epilepsy (TLE). As their seizures are usually self-terminated, the elucidation of the mechanism underlying endogenous seizure termination will help to find a new strategy for epilepsy treatment. We aim to examine the role of inhibitory interneurons in endogenous seizure termination in TLE patients. MethodsWhole-cell recordings were conducted on inhibitory interneurons in seizure-onset cortices of intractable TLE patients and the temporal lobe cortices of nonseizure individuals. The intrinsic property of the inhibitory interneurons and the strength of their GABAergic synaptic outputs were measured. The quantitative data were introduced into the computer-simulated neuronal networks to figure out a role of these inhibitory units in the seizure termination. ResultsIn addition to functional downregulation, a portion of inhibitory interneurons in seizure-onset cortices were upregulated in encoding the spikes and controlling their postsynaptic neurons. A patch-like upregulation of inhibitory neurons in the local network facilitated seizure termination. The upregulations of both inhibitory neurons and their output synapses synergistically shortened seizure duration, attenuated seizure strength, and terminated seizure propagation. ConclusionAutomatic seizure termination is likely due to the fact that a portion of the inhibitory neurons and synapses are upregulated in the seizure-onset cortices. This mechanism may create novel therapeutic strategies to treat intractable epilepsy, such as the simultaneous upregulation of cortical inhibitory neurons and their output synapses.

submitted time 2016-05-11 Hits2846Downloads1365 Comment 0

9. chinaXiv:201605.01333 [pdf]

Spontaneous Vesicle Release Is Not Tightly Coupled to Voltage-Gated Calcium Channel-Mediated Ca2+ Influx and Is Triggered by a Ca2+ Sensor Other Than Synaptotagmin-2 at the Juvenile Mice Calyx of...

Dai, Jinye; Chen, Peihua; Tian, Hao; Sun, Jianyuan; Dai, Jinye; Tian, Hao; Sun, Jianyuan; Chen, Peihua; Sun, Jianyuan
Subjects: Biology >> Biophysics >> Neurosciences

It is well known that voltage-gated calcium channels (VGCCs)-mediated Ca2+ influx triggers evoked synaptic vesicle release. However, the mechanisms of Ca2+ regulation of spontaneous miniature vesicle release (mini) remain poorly understood. Here we show that blocking VGCCs at the juvenile mice (C57BL/6) calyx of Held synapse failed to cause an immediate change in minis. Instead, it resulted in a significant reduction (similar to 40%) of mini frequency several minutes after the blockage. By recording VGCC activity and single vesicle fusion events directly at the presynaptic terminal, we found that minis did not couple to VGCC-mediated Ca2+ entry, arguing for a lack of direct correlation between mini and transient Ca2+ influx. Moreover, mini frequencies displayed a lower apparent Ca2+ cooperativity than those of evoked release. In agreement with this observation, abrogation of the Ca2+ sensor synaptotagmin-2 had no effect on apparent Ca2+ cooperativity of minis. Together, our study provides the first direct evidence that spontaneous minis are not mediated by transient Ca2+ signals through VGCCs and are triggered by a Ca2+-sensing mechanism that is different from the evoked release at these microdomain VGCC-vesicle coupled synapses.

submitted time 2016-05-11 Hits2859Downloads1355 Comment 0

10. chinaXiv:201605.01328 [pdf]

A critical role of temporoparietal junction in the integration of top-down and bottom-up attentional control

Wu, Qiong; Xi, Sisi; Wu, Yanhong; Chang, Chi-Fu; Huang, I-Wen; Juan, Chi-Hung; Liu, Zuxiang; Wu, Yanhong; Wu, Yanhong; Fan, Jin; Fan, Jin; Fan, Jin; Fan, Jin
Subjects: Biology >> Biophysics >> Neurosciences

Information processing can be biased toward behaviorally relevant and salient stimuli by top-down (goal-directed) and bottom-up (stimulus-driven) attentional control processes respectively. However, the neural basis underlying the integration of these processes is not well understood. We employed functional magnetic resonance imaging (fMRI) and transcranial direct-current stimulation (tDCS) in humans to examine the brain mechanisms underlying the interaction between these two processes. We manipulated the cognitive load involved in top-down processing and stimulus surprise involved in bottom-up processing in a factorial design by combining a majority function task and an oddball paradigm. We found that high cognitive load and high surprise level were associated with prolonged reaction time compared to low cognitive load and low surprise level, with a synergistic interaction effect, which was accompanied by a greater deactivation of bilateral temporoparietal junction (TPJ). In addition, the TPJ displayed negative functional connectivity with right middle occipital gyrus, which is involved in bottom-up processing (modulated by the interaction effect), and the right frontal eye field (FEF), which is involved in top-down control. The enhanced negative functional connectivity between the TPJ and right FEF was accompanied by a larger behavioral interaction effect across subjects. Application of cathodal tDCS over the right TPJ eliminated the interaction effect. These results suggest that the TPJ plays a critical role in processing bottom-up information for top-down control of attention. Hum Brain Mapp 36:4317-4333, 2015. (c) 2015 Wiley Periodicals, Inc.

submitted time 2016-05-11 Hits2994Downloads1421 Comment 0

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